Inhibition of ASCT2 is essential in all-trans retinoic acid-induced reduction of adipogenesis in 3T3-L1 cells

Katsuhiko Takahashi; Natsumi Uchida; Chisato Kitanaka; Chiaki Sagara; Masahiko Imai; Noriko Takahashi

doi:10.1016/j.fob.2015.06.012

Inhibition of ASCT2 is essential in all-trans retinoic acid-induced reduction of adipogenesis in 3T3-L1 cells

FEBS Open Bio. 2015 Jul 2:5:571-8. doi: 10.1016/j.fob.2015.06.012. eCollection 2015.

Authors

Katsuhiko Takahashi¹, Natsumi Uchida¹, Chisato Kitanaka¹, Chiaki Sagara¹, Masahiko Imai¹, Noriko Takahashi¹

Affiliation

¹ Laboratory of Physiological Chemistry, Institute of Medicinal Chemistry, Hoshi University, Shinagawa, Tokyo 142-8501, Japan.

Abstract

Vitamin A has preventive effects on obesity. All-trans retinoic acid (ATRA), the active form of vitamin A, inhibits lipid accumulation in 3T3-L1 cells in an experimental adipogenesis model. We found that ATRA suppressed up-regulation of the amino acid transporter, Asct2, in adipogenerating 3T3-L1 cells. We observed that Asct2 was up-regulated at 1 day after adipogenesis stimuli. The Asct2 inhibitor l-γ-glutamyl-p-nitroanilide (GPNA) decreased lipid accumulation. Glutamine-free conditions also suppressed adipogenesis. Suppression of adipogenesis by ATRA may be through Asct2 reduction. These results indicate that Asct2 could be a target for obesity prevention and treatment.

Keywords: ATRA, all-trans retinoic acid; Adipocyte; All-trans retinoic acid; Asct2; DIM, dexamethasone, insulin and 3-isobutylmethylxanthine; FXR, farnesoid X Receptor; GPNA, l-γ-glutamyl-p-nitroanilide; Gapdh, glyceraldehyde 3-phosphate dehydrogenase; Obesity; PPARγ, peroxisome proliferator-activated receptor γ; RAR, retinoic acid receptor; RXR, retinoid X receptor; l-glutamine.